Analysis of GBA gene mutation in three families with Gaucher disease / 临床儿科杂志

Objective To explore the significance of GBA gene mutation and gene detection in diagnosis of Gaucher disease. Method The clinical data and genetic testing results of 3 probands from 3 unrelated Gaucher families and their family members were analyzed. Results A compound heterozygous mutation of c.907C>A and c.1448T>C was found in the proband of the first family, which was inherited from parents respectively. Another complex heterozygous mutation of c.1174delC and c.1226A>G was found in the proband of second family, which was inherited from parents respectively, and the variant c.1174delC was a new mutation, which has not been reported in the literature according to the search by HGMD. The homozygous nucleotide variation of c.1342G>C and heterozygous nucleotide variation of c.1263_1317del was found in the proband of the third family and the c.1263_1317del heterozygous mutation was inherited from father. Conclusion The mutation of GBA gene was the cause of Gaucher disease in these 3 families and Gaucher disease can be diagnosed by molecular genetics in clinic.

Effects of Electroacupuncture Pretreatment on Neurological Function, and Expression of Toll-like Receptor 4 and Nuclear Factor κB in Ischemic Penumbra in Rats after Cerebral Ischemia-reperfusion Injury / 中国康复理论与实践

Objective To investigate the effect of electroacupuncture (EA) pretreatment on neurological function, and the expression of Toll-like receptor 4 (TLR4) and nuclear factorκB (NF-κB) protein in ischemic penumbra after cerebral ischemia-reperfusion (CIR) injury. Methods A total of 36 male Sprague-Dawley rats were randomly divided into sham group (n=12), model group (n=12) and EA group (n=12). The later two groups were occluded their right middle cerebral arteries for two hours and reperfused. The EA group was pretreated with EA at Baihui (GV20) for two weeks before modeling. They were assessed with modified Neurological Severity Scores (mNSS), the injury in ischemic brain was detected with HE staining, and the expression of TLR4 and NF-κB protein in ischemic penumbra were detected with Western blotting, 24 hours after reperfusion. Results The score of mNSS decreased (P<0.05), the injury of brain tissue ameliorated, and the expression of TLR4 and NF-κB decreased in ischemic penumbra (P<0.05) in EA group compared with those in the model group. Conclu-sion EA pretreatment can reduce the injury and improve the neurological function in rats after CIR by down-regulating the expression of TLR4 and NF-κB protein in ischemic penumbra.

Mutational analysis of PHEX,FGF - 23,and DMP - I genes in 4 families patients with familial hypophos-phatemic vitamin D resistant rickets / 中华实用儿科临床杂志

Objective To evaluate the frequency of mutations that occur in PHEX,FGF - 23 and DMP - I genes associated with familial hypophosphatemic vitamin D resistant rickets among 6 patients from 4 families in China. Methods The peripheral blood samples from 4 families were collected and other 10 persons from different families were selected as normal controls,and then the total gene DNA was extracted from the whole blood. Using polymerase chain reaction(PCR)amplication,sequences of the exons and flanking zones in PHEX,FGF - 23 and DMP - I genes were sequenced by direct DNA sequencing and TA cloning,and then the mutations found were analyzed. Results In exon 6 of DMP - I gene,c1218 C ﹥ T and c1230 G ﹥ A mutations were detected in lineage 1,as same sense mutation (propositus and its sister:homozygous mutation;mother:heterozygous mutation);c1333 - 1334 GC ﹥ TT mutation,as missense mutation,was found in exon 12 of PHEX gene on the propositus of lineage 2,determined as heterozygous muta-tion,but the same mutation was not found from their parents. In exon 3 of FGF - 23 gene,c716 C ﹥ T,p. T239M hetero-zygous mutation was found on the propositus and its mother. In exon 6 of the DMP - I gene,c205 A ﹥ T homozygous mutation was detected in lineage 3. In lineage 3,c716 C ﹥ T mutation of the FGF - 23 gene was detected,and the pro-positus and their father had the same mutation. No disease causing mutations of the PHEX,FGF - 23 and DMP - I genes were detected in the family members of lineage 1,3 and 4. Conclusions The mutation c1333 - 1334 GC ﹥ TT detected in exon 12 of PHEX gene might be the cause of disease for the propositus of lineage 2,as missense mutation, which needs further verification;c716 C ﹥ T,p. T239M mutation of the FGF - 23 gene detected in lineage 2 and 3 might not be the causes of the hypophosphatemic rickets and abnormal phenotype.

Analysis of the mutations of SMPD1 gene in Niemann-Pick disease / 临床儿科杂志

Objectives To study the molecular genetics of Niemann-Pick's disease (NPD), and its implication in the diagnosis of NPD. Methods The clinical data and blood samples of three unrelated families were collected. The genomic DNA was extracted from peripheral blood. The six coding exons and their lfanking intronic sequences of SMPD1 gene in all members of three pedigrees were ampliifed by polymerase chain reaction (PCR). The SMPD1 gene sequencing results were compared with the normal sequence from Genbank to identify possible causative mutations. The ampliifcation products of exons where mutations were located were cloned into TA vector for further conifrmation. Results Family 1 proband had homozygous T107C mutation and the parents had heterozygous T107C mutation. The homozygous delete mutation (c.108-113delGCTGGC) was detected and conifrmed by TA cloning in all members of family 2 and 3. The 20 normal control members did not have this delete mutation. Conclusions The genetic basis of NPD in the proband of family 1 is the homozygous T107C mutation in SMPD1 gene, while parents in family 1 are carriers of recessive T107C mutation. The homozygous mutation c.108-113delGCTGGC exists in SMPD1 gene in all members of the family 2 and 3. This delete mutation is considered to be genetic polymorphism.